Substantial acetylcholine reduction in multiple brain regions of Mecp2-deficient female rats and associated behavioral abnormalities.

Rett syndrome (RTT) is a neurodevelopmental disorder with X-linked dominant inheritance caused mainly by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. The effects of various Mecp2 mutations have been extensively assessed in mouse models, but none adequately mimic the symptoms and patho...

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Autores principales:	Hiroyasu Murasawa, Hiroyuki Kobayashi, Jun Imai, Takahiko Nagase, Hitomi Soumiya, Hidefumi Fukumitsu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7c942d7840044a9792c9dfd95d0b0fcd
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spelling	oai:doaj.org-article:7c942d7840044a9792c9dfd95d0b0fcd2021-12-02T20:16:39ZSubstantial acetylcholine reduction in multiple brain regions of Mecp2-deficient female rats and associated behavioral abnormalities.1932-620310.1371/journal.pone.0258830https://doaj.org/article/7c942d7840044a9792c9dfd95d0b0fcd2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258830https://doaj.org/toc/1932-6203Rett syndrome (RTT) is a neurodevelopmental disorder with X-linked dominant inheritance caused mainly by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. The effects of various Mecp2 mutations have been extensively assessed in mouse models, but none adequately mimic the symptoms and pathological changes of RTT. In this study, we assessed the effects of Mecp2 gene deletion on female rats (Mecp2+/-) and found severe impairments in social behavior [at 8 weeks (w), 12 w, and 23 w of age], motor function [at 16 w and 26 w], and spatial cognition [at 29 w] as well as lower plasma insulin-like growth factor (but not brain-derived neurotrophic factor) and markedly reduced acetylcholine (30%-50%) in multiple brain regions compared to female Mecp2+/+ rats [at 29 w]. Alternatively, changes in brain monoamine levels were relatively small, in contrast to reports on mouse Mecp2 mutants. Female Mecp2-deficient rats express phenotypes resembling RTT and so may provide a robust model for future research on RTT pathobiology and treatment.Hiroyasu MurasawaHiroyuki KobayashiJun ImaiTakahiko NagaseHitomi SoumiyaHidefumi FukumitsuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258830 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hiroyasu Murasawa Hiroyuki Kobayashi Jun Imai Takahiko Nagase Hitomi Soumiya Hidefumi Fukumitsu Substantial acetylcholine reduction in multiple brain regions of Mecp2-deficient female rats and associated behavioral abnormalities.
description	Rett syndrome (RTT) is a neurodevelopmental disorder with X-linked dominant inheritance caused mainly by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. The effects of various Mecp2 mutations have been extensively assessed in mouse models, but none adequately mimic the symptoms and pathological changes of RTT. In this study, we assessed the effects of Mecp2 gene deletion on female rats (Mecp2+/-) and found severe impairments in social behavior [at 8 weeks (w), 12 w, and 23 w of age], motor function [at 16 w and 26 w], and spatial cognition [at 29 w] as well as lower plasma insulin-like growth factor (but not brain-derived neurotrophic factor) and markedly reduced acetylcholine (30%-50%) in multiple brain regions compared to female Mecp2+/+ rats [at 29 w]. Alternatively, changes in brain monoamine levels were relatively small, in contrast to reports on mouse Mecp2 mutants. Female Mecp2-deficient rats express phenotypes resembling RTT and so may provide a robust model for future research on RTT pathobiology and treatment.
format	article
author	Hiroyasu Murasawa Hiroyuki Kobayashi Jun Imai Takahiko Nagase Hitomi Soumiya Hidefumi Fukumitsu
author_facet	Hiroyasu Murasawa Hiroyuki Kobayashi Jun Imai Takahiko Nagase Hitomi Soumiya Hidefumi Fukumitsu
author_sort	Hiroyasu Murasawa
title	Substantial acetylcholine reduction in multiple brain regions of Mecp2-deficient female rats and associated behavioral abnormalities.
title_short	Substantial acetylcholine reduction in multiple brain regions of Mecp2-deficient female rats and associated behavioral abnormalities.
title_full	Substantial acetylcholine reduction in multiple brain regions of Mecp2-deficient female rats and associated behavioral abnormalities.
title_fullStr	Substantial acetylcholine reduction in multiple brain regions of Mecp2-deficient female rats and associated behavioral abnormalities.
title_full_unstemmed	Substantial acetylcholine reduction in multiple brain regions of Mecp2-deficient female rats and associated behavioral abnormalities.
title_sort	substantial acetylcholine reduction in multiple brain regions of mecp2-deficient female rats and associated behavioral abnormalities.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/7c942d7840044a9792c9dfd95d0b0fcd
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Substantial acetylcholine reduction in multiple brain regions of Mecp2-deficient female rats and associated behavioral abnormalities.

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